The present invention relates to a series of new anilino-substituted cyclopenta[d]pyrimidine derivatives having valuable antidepressant activity, to a process for preparing these compounds and to a pharmaceutical composition containing them.
A variety of compounds having antidepressant activity is known and many of these are used in the treatment of mental depression. The compounds mainly used for this purpose are commonly classified into two groups: the "monoamine oxidase inhibitors", which are mostly hydrazine derivatives; and the "tricyclic antidepressants", which mainly have a dibenzazepine or dibenzocycloheptene structure ["Martindale: The Extra Pharmacopoeia", twenty-seventh Edition (1977), published by the Pharmaceutical Press, London]. Of these classes, the tricyclic antidepressants are generally considered to be more effective than the monoamine oxidase inhibitors and are therefore preferred; one of the most preferred of the tricyclic antidepressants in current use is imipramine. All of the currently available antidepressants exhibit a variety of side-effects of varying degrees of seriousness, which result in their use being somewhat restricted. Imipramine, for example, exhibits antihistaminic and anticholinergic activities.
The known classes of antidepressant, however, have a totally different molecular structure from the compounds of the invention.
A class of antidepressant pyrimidine derivatives, including some related to the compounds of the invention, is disclosed in U.S. Pat. No. 4,450,162. The majority of the compounds disclosed in that U.S. Pat. are simple pyrimidine derivatives. However, included amongst them are some cyclopenta[d]pyrimidine derivatives which differ from those of the present invention in having hydrogen atoms at all of the 5, 6 and 7 positions of the cyclopenta[d]pyrimidine nucleus, whereas the compounds of the present invention have hydroxy or substituted hydroxy groups at one or two of these positions.
It is believed that at least one of the compounds of the invention--that of formula (I) given below, where R.sup.1 =OH, R.sup.2 =H, R.sup.3 =H, R.sup.4 =4-CN and R.sup.5 =H--may be a product of the canine metabolism of the corresponding prior art compound corresponding to formula (I) given below but where R.sup.1 =H, as the compound of the invention has been isolated by us from the urine of a dog to which the prior art compound had been orally administered.